PMID- 35078917
OWN - NLM
STAT- MEDLINE
DCOM- 20220531
LR  - 20231101
IS  - 1468-330X (Electronic)
IS  - 0022-3050 (Print)
IS  - 0022-3050 (Linking)
VI  - 93
IP  - 6
DP  - 2022 Jun
TI  - Differential levels of plasma biomarkers of neurodegeneration in Lewy body 
      dementia, Alzheimer's disease, frontotemporal dementia and progressive 
      supranuclear palsy.
PG  - 651-658
LID - 10.1136/jnnp-2021-327788 [doi]
AB  - OBJECTIVES: This longitudinal study compared emerging plasma biomarkers for 
      neurodegenerative disease between controls, patients with Alzheimer's disease 
      (AD), Lewy body dementia (LBD), frontotemporal dementia (FTD) and progressive 
      supranuclear palsy (PSP). METHODS: Plasma phosphorylated tau at threonine-181 
      (p-tau181), amyloid beta (Alphabeta)42, Abeta40, neurofilament light (NfL) and glial 
      fibrillar acidic protein (GFAP) were measured using highly sensitive single 
      molecule immunoassays (Simoa) in a multicentre cohort of 300 participants 
      (controls=73, amyloid positive mild cognitive impairment (MCI+) and AD 
      dementia=63, LBD=117, FTD=28, PSP=19). LBD participants had known positron 
      emission tomography (PET)-Abeta status. RESULTS: P-tau181 was elevated in MCI+AD 
      compared with all other groups. Abeta42/40 was lower in MCI+AD compared with 
      controls and FTD. NfL was elevated in all dementias compared with controls while 
      GFAP was elevated in MCI+AD and LBD. Plasma biomarkers could classify between 
      MCI+AD and controls, FTD and PSP with high accuracy but showed limited ability in 
      differentiating MCI+AD from LBD. No differences were detected in the levels of 
      plasma biomarkers when comparing PET-Abeta positive and negative LBD. P-tau181, NfL 
      and GFAP were associated with baseline and longitudinal cognitive decline in a 
      disease specific pattern. CONCLUSION: This large study shows the role of plasma 
      biomarkers in differentiating patients with different dementias, and at 
      monitoring longitudinal change. We confirm that p-tau181 is elevated in MCI+AD, 
      versus controls, FTD and PSP, but is less accurate in the classification between 
      MCI+AD and LBD or detecting amyloid brain pathology in LBD. NfL was elevated in 
      all dementia groups, while GFAP was elevated in MCI+AD and LBD.
CI  - (c) Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published 
      by BMJ.
FAU - Chouliaras, Leonidas
AU  - Chouliaras L
AUID- ORCID: 0000-0002-3052-3879
AD  - Department of Psychiatry, University of Cambridge School of Clinical Medicine, 
      Cambridge, UK lc716@medschl.cam.ac.uk.
FAU - Thomas, Alan
AU  - Thomas A
AD  - Translational and Clinical Research Institute, Newcastle University, Newcastle, 
      UK.
FAU - Malpetti, Maura
AU  - Malpetti M
AUID- ORCID: 0000-0001-8923-9656
AD  - Department of Clinical Neurosciences, University of Cambridge School of Clinical 
      Medicine, Cambridge, UK.
FAU - Donaghy, Paul
AU  - Donaghy P
AD  - Translational and Clinical Research Institute, Newcastle University, Newcastle, 
      UK.
FAU - Kane, Joseph
AU  - Kane J
AD  - Centre for Public Health, Queen's University Belfast, Belfast, UK.
FAU - Mak, Elijah
AU  - Mak E
AD  - Department of Psychiatry, University of Cambridge School of Clinical Medicine, 
      Cambridge, UK.
FAU - Savulich, George
AU  - Savulich G
AD  - Department of Psychiatry, University of Cambridge School of Clinical Medicine, 
      Cambridge, UK.
FAU - Prats-Sedano, Maria A
AU  - Prats-Sedano MA
AD  - Department of Psychiatry, University of Cambridge School of Clinical Medicine, 
      Cambridge, UK.
FAU - Heslegrave, Amanda J
AU  - Heslegrave AJ
AD  - Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, 
      London, UK.
AD  - Dementia Research Insitute, UCL, London, UK.
FAU - Zetterberg, Henrik
AU  - Zetterberg H
AUID- ORCID: 0000-0003-3930-4354
AD  - Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, 
      London, UK.
AD  - Dementia Research Insitute, UCL, London, UK.
AD  - Department of Psychiatry and Neurochemistry, Institute of Neuroscience and 
      Physiology, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, 
      Sweden.
AD  - Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Molndal, 
      Sweden.
AD  - Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China.
FAU - Su, Li
AU  - Su L
AD  - Department of Psychiatry, University of Cambridge School of Clinical Medicine, 
      Cambridge, UK.
AD  - Department of Neuroscience, University of Sheffield, Sheffield, UK.
FAU - Rowe, James Benedict
AU  - Rowe JB
AUID- ORCID: 0000-0001-7216-8679
AD  - Department of Clinical Neurosciences, University of Cambridge School of Clinical 
      Medicine, Cambridge, UK.
AD  - Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
FAU - O'Brien, John Tiernan
AU  - O'Brien JT
AD  - Department of Psychiatry, University of Cambridge School of Clinical Medicine, 
      Cambridge, UK.
AD  - Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.
LA  - eng
GR  - WT_/Wellcome Trust/United Kingdom
GR  - 220258/WT_/Wellcome Trust/United Kingdom
GR  - MR/M009041/1/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20220125
PL  - England
TA  - J Neurol Neurosurg Psychiatry
JT  - Journal of neurology, neurosurgery, and psychiatry
JID - 2985191R
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Biomarkers)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (tau Proteins)
SB  - IM
CIN - doi: 10.1136/jnnp-2021-328649
MH  - *Alzheimer Disease/diagnosis
MH  - Amyloid beta-Peptides
MH  - Biomarkers
MH  - *Cognitive Dysfunction/diagnosis
MH  - *Frontotemporal Dementia/diagnosis
MH  - Glial Fibrillary Acidic Protein
MH  - Humans
MH  - *Lewy Body Disease/diagnosis
MH  - Longitudinal Studies
MH  - *Neurodegenerative Diseases
MH  - *Supranuclear Palsy, Progressive/diagnosis
MH  - tau Proteins
PMC - PMC9148982
MID - EMS142453
OTO - NOTNLM
OT  - alzheimer's disease
OT  - dementia
OT  - frontotemporal dementia
OT  - lewy body dementia
OT  - movement disorders
COIS- Competing interests: Competing interests unrelated to this work, JBR serves as an 
      associate editor to Brain and is a non-remunerated trustee of the Guarantors of 
      Brain, Darwin College and the PSP Association (UK). He provides consultancy to 
      Asceneuron, Biogen, UCB and has research grants from AZ-Medimmune, Janssen, Lilly 
      as industry partners in the Dementias Platform UK. Unrelated to this work, JTOB 
      has received honoraria for work as DSMB chair or member for TauRx, Axon, Eisai, 
      has acted as a consultant for Roche, and has received research support from 
      Alliance Medical and Merck. HZ has served at scientific advisory boards and/or as 
      a consultant for Alector, Eisai, Denali, Roche Diagnostics, Wave, Samumed, 
      Siemens Healthineers, Pinteon Therapeutics, Nervgen, AZTherapies, CogRx and Red 
      Abbey Labs, has given lectures in symposia sponsored by Cellectricon, Fujirebio, 
      Alzecure and Biogen, and is a co-founder of Brain Biomarker Solutions in 
      Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program 
      (outside submitted work). Avid Radiopharmaceuticals, a wholly owned subsidiary of 
      Eli Lilly and Company, enabled use of the 18F-florbetapir by providing tracer and 
      funding scanner time, but was not involved in data analysis or interpretation.
EDAT- 2022/01/27 06:00
MHDA- 2022/06/01 06:00
PMCR- 2022/05/30
CRDT- 2022/01/26 05:28
PHST- 2021/08/10 00:00 [received]
PHST- 2021/12/01 00:00 [accepted]
PHST- 2022/01/27 06:00 [pubmed]
PHST- 2022/06/01 06:00 [medline]
PHST- 2022/01/26 05:28 [entrez]
PHST- 2022/05/30 00:00 [pmc-release]
AID - jnnp-2021-327788 [pii]
AID - 10.1136/jnnp-2021-327788 [doi]
PST - ppublish
SO  - J Neurol Neurosurg Psychiatry. 2022 Jun;93(6):651-658. doi: 
      10.1136/jnnp-2021-327788. Epub 2022 Jan 25.